How To Pin Down 55,000 Virus Particles

How To Pin Down 55,000 Virus Particles

Researchers have made an array of 55,000 pens that can simultaneously draw 55,000 identical nanoscale images. (Courtesy of Chad Mirkin, Northwestern University)

Researchers have developed a device that uses 55,000 perfectly aligned, microscopic pens to write patterns with features the size of viruses. The tool could allow researchers to study the behavior of cells at a new rate of speed and level of detail, potentially leading to better diagnostics and treatments for diseases such as cancer.

The device builds on a technique called dip-pen nanolithography, which was first developed in 1999 by Chad Mirkin, professor of chemistry, medicine, and materials science and engineering at Northwestern University. In that system, the tip of a single atomic force microscope (AFM) probe is dipped in selected molecules, much as a quill pen would be dipped in ink. Then the molecules slip from the tip of the probe onto a surface, forming lines or dots less than 100 nanometers wide. Their size is controlled by the speed of the pen.

Because it operates at room temperature, the dip-pen tool is particularly useful for working with biological materials, such as proteins and segments of DNA that would be damaged by high-energy methods like electron beam lithography. Also, the patterns it makes can be easily programmed, making it “probably the best rapid-prototyping system for nanostructures out there,” Mirkin says.

The method addresses “one of the biggest problems in nanoscience,” according to Mirkin. “How do I get fingers small enough to manipulate something so small I can only see it with an electron microscope?” Because the tool can work at that scale “routinely,” he says, “I think it’s going to turn everything upside-down.”

So far, applications of the single-pen device, which is already being sold through NanoInk, a company based in Chicago, have been limited because of the speed of the process. “The drawback of [dip-pen nanolithography] in its early years was that it was slow if you wanted to prepare substrates that were patterned over large areas,” on the scale of a square centimeter, says Milan Mrksich, professor of chemistry at the University of Chicago (who was not involved with the work).

Mirkin and colleagues have overcome this problem by creating a massive array of pens using conventional photolithography. “The 55,000-pen array greatly accelerates the patterning rate,” Mrksich says, “increasing the throughput by orders of magnitude.” Mirkin says the pens can now write “hundreds of millions of features on a minute time-scale.”

In a paper appearing online now in the journal Angewandte Chemie, Mirkin described test runs with the array that show the complexity of the patterns that are possible. For example, he simultaneously printed 55,000 identical microscopic nickels in an area smaller than a dime. The dots outlining Jefferson’s face are each only 80 nanometers wide.